Navajo men who were underground miners have excess risk of lung cancer. To further characterize the long-term consequences of uranium mining in this high-risk population, we examined lung cancer incidence among Navajo men residing in New Mexico and Arizona from 1969 to 1993 and conducted a population-based case-control study to estimate the risk of lung cancer for Navajo uranium miners. Uranium mining contributed substantially to lung cancer among Navajo men over the 25-year period following the end of mining for the Navajo Nation. Sixty-three (67%) of the 94-incident lung cancers among Navajo men occurred in former uranium miners. The relative risk for a history of mining was 28.6 (95% confidence interval, 13.2–61.7). Smoking did not account for the strong relationship between lung cancer and uranium mining. The Navajo experience with uranium mining is a unique example of exposure in a single occupation accounting for the majority of lung cancers in an entire population.